ArticleCell death & disease2018
Protease-activated receptor 2 signaling modulates susceptibility of colonic epithelium to injury through stabilization of YAP in vivo.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Monoclonal antibody inhibition of PAR2 reduces phenotype severity and pain in murine inflammatory bowel disease.Pain reports · 2026Article
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 2026Review
- Article
- CD2 expressing innate lymphoid and T cells are critical effectors of immunopathogenesis in hidradenitis suppurativa.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Par2-mediated responses in inflammation and regeneration: choosing between repair and damage.Inflammation and regeneration · 2024Review
- Low-Dose Trypsin Accelerates Wound HealingACS pharmacology & translational science · 2024Article
- Development of a 32-gene signature using machine learning for accurate prediction of inflammatory bowel disease.Cell regeneration (London, England) · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- PAR-2-activated secretion by airway gland serous cells: role for CFTR and inhibition byAmerican journal of physiology. Lung cellular and molecular physiology · 2021Article
- Review
- Blockage of protease-activated receptor 2 exacerbates inflammation in high-fat environment partly through autophagy inhibition.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- It takes two to tango: coupling of Hippo pathway and redox signaling in biological process.Cell cycle (Georgetown, Tex.) · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hippo signaling plays critical roles in intestinal regeneration. However, the mechanisms which regulate its activity in vivo are largely unknown. We hypothesize that protease-activated receptor 2 (PAR2) signaling, which could be activated by trypsin, might affect YAP activity in the setting of tissue damage and regeneration. It is found that knockout of PAR2 severely aggravates the mucosal damage induced by dextran sodium sulfate (DSS) in mouse, which correlated with notable repression of YAP protein in colonic epithelial cells. Although the cytokine expression is reduced, the damage of colonic crypt is more severe after DSS-induced colitis in PAR2-/- mouse. In vitro, PAR2 activation causes the accumulation of YAP, while knockdown of PAR2 with shRNA dramatically represses the expression of YAP protein in different intestinal epithelial cell lines. Moreover, forced expression of YAP significantly reduces the production of reactive oxygen species (ROS) and the sensitivity to nitric oxide-induced apoptosis in PAR2-deficient condition. Further studies show that PAR2 signaling stabilizes YAP protein but independent of Lats. Nevertheless PAR2 activation increased the binding of YAP with protein phosphatase PP1. Inhibition of PP1 with specific siRNA blocked PAR2-induced dephosphorylation of YAP. Taken together, PAR2 signaling might modulate susceptibility of colonic epithelium to injury through stabilization of YAP.
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